Rationale Mutations in the DJ-1 gene are a cause of familial Parkinson's disease. Dopaminergic neurones deficient in DJ-1 have impaired mitochondrial function and are more susceptible to oxidative stress. DJ-1 is present in the heart but its role there is unknown. Given its beneficial mitochondrial effects, we hypothesised that DJ-1 protects the heart against acute ischaemia-reperfusion injury (IRI).

Methodology The murine cardiac HL-1 cell line was transfected with either empty vector, wild-type DJ-1, mitochondrial-targeted DJ-1 or the L166P mutant DJ-1 (which is unable to dimerise and translocate to mitochondria) and the effects on mitochondrial morphology, the susceptibility to mitochondrial permeability transition pore (mPTP) opening, and cell survival following simulated IRI, were investigated.

Results Overexpressing wild type and mitochondrial-targeted DJ-1 in the HL-1 cardiac cells induced elongation of mitochondria (to a similar extent as the mitochondrial fusion protein Mfn1); reduced the susceptibility to mPTP opening (to a similar extent as cyclosporin A, a known mPTP inhibitor); and improved cell survival following simulated IRI. Early indications suggest that these beneficial effects on mitochondrial function are absent in the L166P mutant DJ-1.

Conclusion We show a novel role for DJ-1 in the heart. It appears to protect the heart from IRI and this effect is associated with changes in mitochondrial morphology and mPTP inhibition.